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Biomedical subjects

E Thiel

Publications and source records attributed to E Thiel.

At least 289 records · Page 16Linked to original sources

Specific translocation t(4;11) in an infant with acute lymphoblastic leukaemia of null cell type.

A case of acute lymphoblastic leukaemia of null cell type in infancy showed the specific reciprocal translocation t(4;11) (q21;q23) reported 16 times so far in the world literature. The proportions of abnormal and normal metaphases throughout the course of the illness correlated well with the clinical picture, but even during the short term remission metaphases expressing the translocation were still identifiable in appreciable numbers. Comparison between cytogenetic analyses of cultured and native bone marrow, PHA-stimulated and non-stimulated peripheral blood demonstrated the gradual conquest of the periphery by the abnormal clone. The importance of chromosomal changes and their interpretation for diagnosis, classification and prognostic judgment in haemotologic neoplasms is discussed in the light of the reported case.

Bone Marrow Cells↗

Immunofluorescence with monoclonal antibodies on poly-L-lysine coated slides: an alternative to conventional methods.

It is sometimes difficult to perform immunofluorescence tests because of low cell numbers. Therefore a simple method using poly-L-lysine coated slides was applied to immunofluorescence and compared with the routine suspension method. Peripheral blood lymphocytes from normal persons, samples of normal bone marrow, thymus and tonsil as well as samples from patients with leukemia or lymphoma were tested with these two methods using 20 different monoclonal antibodies. The PLL-slide method was shown to be comparable with the suspension method and is an alternative in case of low cell numbers, since as few as 3 X 10(4) cells can be tested for one antigen.

Antibodies, Monoclonal↗

[Recruiting patients and results of a preliminary study on the therapy of acute lymphatic leukemia and acute undifferentiated leukemia in adults].

The aim of the study was to improve remission quality through application of an intensified induction therapy successful in childhood ALL; in a modified form for patients of 15-35 years and in a reduced form for patients of greater than 35-65 years with ALL or AUL. The 8-week induction therapy consists of two phases. In phase I, prednisone, vincristine, daunorubicin, and L-asparaginase are given and in phase II, cyclophosphamide, cytosine-arabinoside, and 6-mercaptopurinee. As CNS-prophylaxis, intrathecal methotrexate, and CNS-irradiation with 24 Gy are used. After 3 months a re-induction therapy similar to the induction therapy is given with dexamethasone and adriamycin instead of prednisone and daunorubicin and without L-asparaginase. Maintenance therapy with 6-mercaptopurin and methotrexate follows over a period of 2 years. Since the formation of the study group in 1979 up to 30.06.81, 170 patients from 25 hospitals with newly diagnosed ALL or AUL were treated according to the protocol. Up to 30.11.81, 162 patients had completed treatment and were evaluable. Of these, 77.8% achieved complete remission, 80.7% in the age group 15-35 years and 68.3% in the age group greater than 35-65 years. The median survival time for all patients was 24 months and for the 126 patients with complete remission the median has not yet been reached (last observation 31 months). The median remission duration is 20 months. Prognostic factors for remission duration are (1) the number of chemotherapy courses required to reach complete remission, (2) the immunological subtype, (3) age and (4) initial leukocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Analysis with monoclonal antibodies of human lymphoid cells forming rosettes with rabbit red blood cells.

Rabbit red blood cells have previously been shown to rosette with a subpopulation of thymocytes and with mitogen activated peripheral lymphocytes but not with unstimulated lymphocytes. Using monoclonal antibodies and double marker assays we studied the phenotype of these cells. In thymus, over 90% of rosetting cells express antigens of immature thymocytes (HTA1, OKT6). A proportion of the rosetting cells shows in addition antigens of mature thymocytes (OKT3, UCHT1). These cells probably correspond to a stage of intrathymic maturation between common and mature thymocytes. Virtually all rosetting cells are T cells and express an antigen related to T cell activation (TAC) when lymphocytes are activated by mitogens like PHA or Con A. Few rosetting cells are Ia positive. Two other antigens (OKT9, OKT10) known to be associated with proliferating and immature cells, are found in variable proportions on rosetting cells. After stimulation with allogeneic lymphocytes, fewer rosettes are detected than after stimulation by mitogens. Cells activated by a soluble antigen (PPD) and forming rosettes with rabbit red blood cells have a helper phenotype (Leu3a positive). Screening of leukaemia cell samples revealed that only cells from patients with T-ALL form rosettes with rabbit red blood cells. Rosette formation is almost totally inhibited by a polyclonal anti-thymocyte serum and two monoclonal antibodies (OKT11A,Lyt3) which have been shown to block rosettes with sheep erythrocytes.

Animals↗

Proliferation of T gamma-lymphocytes in two patients: clinical features and functional properties of the proliferating cells.

Two patients suffering form proliferation of T gamma cells exhibited uncommon clinical features, such as activation of intravascular coagulation after low dose irradiation of the enlarged spleen in one patient and isolated neutropenia in the other patients. While the malignant nature of the disease was doubtless in one patient, cell proliferation in the other patient was more likely reactive. In addition to T cell determinants the proliferating cells expressed a monocytic antigen. They did not suppress B-lymphocyte differentiation into plasma cells. In contrast the proliferating cell, especially in one patient, acted as potent effectors in NK and ADCC using melanoma and MOLT 4 target cells. Erythrophagocytosis by T gamma cells was seen in one patient. The data suggest that subsets of T gamma cells are related to the monocytic lineage and that these cells cen mediate both NKA and ADCC and partly can develop phagocytic activity.

Aged↗

Comparison of currently available monoclonal antibodies with conventional markers for phenotyping of one hundred acute leukemias.

One hundred acute leukemia cell samples (89 ALL, 11 AMML) derived from children's bone marrow at diagnosis were typed for the reaction with 15 monoclonal antibodies (mAbs). Subdivision in ALL-subgroups was performed according to conventional markers. Only some mAbs like VIL-Al which is directed against the cALL-antigen, can substitute polyclonal rabbit antisera. Additional subclassifications became evident by the use of mAbs for T-cell differentiated ALL forms. However, unexpected negative reactions must be taken into account as observed for all T-directed mAbs with individual T-cell ALL samples.

Acute Disease↗

Protein synthesis in the blood lymphocytes of chronic lymphocytic leukemia and its relationship to prognosis.

Protein synthesis primed by endogenous messenger RNA (mRNA) as well as polyuridylic acid-[poly (U)] directed polyphenylalanine synthesis was measured in extracts of blood lymphocytes from a series of 50 chronic lymphocytic leukemia (CLL) patients and compared with the prognostic stage. Patients were clinically classified according to the new international workshop classification [4]. There were 23 patients at stage A, 14 at stage B and 13 at stage C. Extracts from patients of the high risk group (stage C), defined by anemia and/or thrombocytopenia, exhibited a significantly higher poly (U)-translation activity than extracts from low and intermediate risk patients-stages A and B--(P less than 0.01). This finding has a sensitivity of 62% but a specificity of 100%. During follow-up, an increase of poly (U)-translation and endogenous protein synthesis was observed after changing from stages A or B to stage C. Activity of protein synthesis could neither be correlated with proliferation activity, as measured by lymphocyte doubling time, nor with the expression of immunologic surface markers, nor with serum immunoglobulin (Ig) levels.

Acute Disease↗

Ph1 -positive CML associated with megakaryocytic hyperplasia and thrombocythemia and an abnormality of chromosome no. 3.

A patient with Philadelphia (Ph1) chromosome positive chronic myelocytic leukemia is described, who had in blast crisis in addition an abnormality of chromosome No. 3; ins(3; 3)(q26; q21q26). This abnormality might be connected with hyperplasia of megakaryocytes and thrombocythemia, as recently reported in patients with acute leukemia. In the initial phase of the disease our patient had also thrombocythemia, hyperplasia of megakaryocytes with morphological abnormalities. Furthermore, when blast cells were culture in diffusion chambers, differentiation into several cell lines occurred but not into megakaryopoiesis. It is, therefore, concluded that the involved band on chromosome No. 3 might contain the locus which controls megakaryocytic proliferation and platelet production but additional factors seem to be required for their expression.

Bone Marrow↗

Purification of human monocytes by adherence to polymeric fluorocarbon. Characterization of the monocyte-enriched cell fraction.

Human mononuclear cells were obtained from peripheral blood by density gradients. Monocytes can be purified after cultivation of 2 hours by a modified adherence procedure on membranes of gas-permeable polymeric fluorocarbon (teflon). After further cultivation of 24-48 hours, monocyte-enriched cell fraction can be easily detached from the membranes with a viability greater than 98% and a final cell yield of approximately 50% of the peripheral monocyte count. The cells showed the morphological and cytochemical characteristics of human monocytes and differentiated into dense monolayers of macrophages within 10 days of cultivation. Immune-autoradiography with iodine-125-labelled xenogeneic antimonocytic antisera and staining with several monoclonal antisera in an indirect immunofluorescence technique revealed up to 92% of these cells to carry monocytic characteristics. To show their functional integrity, monocytes obtained by this procedure were activated by 48 hours' cultivation with synthetic alkyl-lysophospholipids to inhibit the proliferation of autologous tumor cells.

Autoradiography↗

Chronic leukemia with a hybrid surface phenotype (T lymphocytic/myelomonocytic): leukemic cells displaying natural killer activity and antibody-dependent cellular cytotoxicity.

A patient with chronic leukemia exhibited uncommon clinical features, such as hypergammaglobulinemia and activation of intravascular coagulation after low-dose irradiation of the enlarged spleen. By light and electron microscopy, the leukemic cells resembled large granular lymphocytes. The following markers were simultaneously expressed on their surface: receptors for sheep erythrocytes and the Fc part of IgG; common T-cell antigens as revealed by a heteroantiserum (HuTLA) and monoclonal antibodies (OKT3, T411); antigens shared by cytotoxic/suppressor T cells (OKT8, T811) as well as myelomonocytic antigens defined by the OKM1 and M522 monoclonal antibodies. The leukemic cells showed both spontaneous (NK) and antibody-dependent (ADCC) cytotoxicity, but they did not suppress B-cell differentiation in vitro.

Aged↗

[Bone marrow transplantation for aplastic anaemia (author's transl)].

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

Adolescent↗

Auer bodies in acute lymphocytic leukaemia and B-cell lymphoma: evidence for a common progenitor of myeloid and lymphoid cells?

In a patient with acute lymphocytic leukaemia (pre-T ALL) and another patient with leukaemic generalization of B-cell lymphoma Auer bodies were found in a few immature cells. The diagnosis in both cases was based on clinical grounds, morphology, cytochemistry, and immunological marker analysis of the blasts. Auer bodies are known to be a marker of high significance for acute non-lymphocytic leukaemias. Therefore the findings described suggest mixed leukaemias with either T-cell or B-cell predominance. It provides further evidence for the existence of a common progenitor of myeloid and lymphoid cells.

Adolescent↗

Appearance of B- or T-lymphocyte markers after diffusion chamber culture of acute lymphoblastic leukemia cells.

Blast cells derived from blood and marrow samples of a patient with acute lymphoblastic leukemia (ALL), as well as from the Reh line originally established from an ALL patient, were cultured in diffusion chambers implanted i.p. into preirradiated CBA mice. At different intervals over a period of up to 20 days, surface immunoglobulins, ALL antigen, and T-cell antigen were investigated by using direct immunofluorescence. Rosette formation was tested with sheep and mouse erythrocytes. On day 0, the cells expressed only ALL antigen at the surface, and no rosette formation was observed. During culture the patient's lymphoblasts, which originally had cytoplasmic IgM in addition to ALL antigen, expressed surface immunoglobulins as well as mouse erythrocyte receptors. The Reh line cells were ambivalent in two experiments developing T-cell antigens and sheep erythrocyte receptors as well as mouse erythrocyte receptors. Our data suggest that the differentiation arrest in leukemic lymphoblasts can be overcome, thus entailing a surface pattern similar to mature T- or B-lymphocytes.

Antigens↗

Tritium radiolabeling of antibodies to high specific activity with N-succinimidyl [2,3-3H] propionate: use in detecting monoclonal antibodies.

A simple method has been established for tritium labeling immunoglobulins. This label avoids certain disadvantages of 125iodine such as high radiation hazard and requirement for frequent labeling owing to the short half-life of this isotope. High specific activities (range 1.8-9.0 cpm/mu g protein) were obtained with no loss of functional activity as demonstrated by passive hemagglutination. The labeled conjugate is especially suitable for detection of activity in hybridoma supernatants by indirect binding assay. Adapted to microtiter plates, the method is suitable for large numbers of samples, e.g. up to 800 supernatants may be examined daily. The utility and advantages of the binding assay with respect to reproducibility, sensitivity, binding kinetics, easy and rapid performance are described.

Animals↗

Cytochemistry and membrane markers in acute lymphatic leukaemia (ALL).

136 patients suffering from ALL were subdivided into 5 subtypes (C-ALL, C/T-ALL, pre-T-ALL, B-ALL) according to rosetting tests and using specific antisera directed against membrane antigens. In addition, leukaemic blasts of all patients were investigated according to morphological and cytochemical criteria. In APh and ANAE, indices and the percentages of cases showing a granular staining pattern were high in pre-T- and in T-ALL, but low in C/T- and in C-ALL. PAS-staining, conversely, was more pronounced in C/T- and C-ALL. APh proved to be more discriminative for recognition of the T- and pre-T-ALL subgroups than ANAE, but ANAE-cytochemistry may be useful to detect contaminating normal T-lymphocytes in ALL. Receptors for C3 were more frequent in C- and in T-ALL than in C/T- and in pre-T-ALL, receptors for Fc were distributed equally among all subtypes. Positively of C3- and Fc-receptors was not correlated with cytochemical results. Morphological criteria were not sufficient for subclassification of ALL; the combination of APh- and PAS-staining, however, is valuable to differentiate between C-subgroups and T-subgroups.

Acid Phosphatase↗